Beyond cell capture: antibody conjugation improves hemocompatibility for vascular tissue engineering applications.

Abstract

Antibody-conjugated surfaces are being studied for cardiovascular implant applications to capture endothelial progenitor cells and promote endothelialization. However, despite the large amount of literature on endothelial progenitor cell capture efficiency, little effort has been made to understand acute blood responses to the modified surfaces. We hypothesize that CD34 antibody conjugation passivates surfaces against procoagulatory events, and thus improves hemocompatibility. To test this hypothesis, we subjected the modified films to hemocompatibility tests to evaluate contact activation, platelet adhesion and activation, as well as whole blood clotting response to the films. Here, we demonstrate the alteration of blood responses due to polyacrylic acid (PAAc) engraftment and subsequent antibody conjugation on biaxially stretched polycaprolactone (PCL) films. Compared to PCL, PAAc-engrafted PCL (PCL-PAAc) and CD34-antibody-conjugated films (PCL-PAAC-CD34) resulted in a four- to ninefold (p < 0.001) reduced platelet activation. PCL-PAAc, however, resulted in an increased contact activation on thromboelastography, and a poorer blood compatibility index assay (43.4% +/- 2.3% vs. 60.9% +/- 2.5%, p < 0.05). PCL-PAAC-CD34, on the other hand, resulted in delayed clot formation (r = 19.3 +/- 1.5, k = 6.8 +/- 0.6 min) and reduced platelet adhesion and activation, and yielded the highest blood compatibility index score, indicating least thrombogenicity (69.3% +/- 3.2%). Our results suggest that CD34 antibody conjugation significantly improved the hemocompatibility of PAAc-conjugated PCL.